The proposed research will determine how neurological mutations can alter the morphology of individual identified neurons in the fruit fly, Drosophila melanogaster. Two classes of mutations will be investigated: (1) behavioral mutations affecting flight motor output, several of which are currently known to modify neuronal function in specific neural pathways of the thoracic ganglion; and (2) homeotic mutations of the bithorax gene complex, which are known to affect developmental regulation of segmentation in the thorax, including at least some aspects of neural organization. Identified neurons of the thoracic nervous system will be examined in the mutant flies to discover what cellular changes accompany the altered genome. The principal method for this study shall be light and electron microscopy of plastic embedded, serially sectioned specimens. This procedure is chosen to permit high resolution analysis while requiring only routine processing of the material. A detailed characterization of neurons in the thoracic nervous system of the wild-type fly shall provide the necessary background for the examination of neurological mutants. Using this approach, preliminary study of the giant fiber pathway in normal flies has already demonstrated that specific neurons and even specific synapses can be readily located and identified. Continued application of this approach has begun to yield not only further detailed description of normal neuronal anatomy but also recognition of specific mutant transformations of individual cells. The long term goal of this research is an understanding of the mechanisms by which the complex structure of the nervous system is programmed in an animal's genes and assembled through development. Such investigation into the genetic control of neuronal organization may eventually lead, through an understanding of the underlying causes, to a rational therapy for or prevention of genetic and congenital defects of the nervous system.